Isochlorogenic acid B alleviates lead-induced anxiety, depression and neuroinflammation in mice by the BDNF pathway

Lead (Pb) can cause neurobehavioral abnormalities. Isochlorogenic acid B (ICAB), a dietary flavonoid found in tea, sweet potato, artichoke, propolis and several plants, exhibited potential neuroprotective properties. In this study, we aimed to investigate the mechanisms of Pb-induced anxiety, depression and neuroinflammation, and the neuroprotective effect of ICAB in mouse brains. We found that ICAB supplementation significantly improved behavioral abnormalities, neuroinflammation and oxidative stress induced by Pb. ICAB attenuated Pb-induced anxiety and depression behavior in mice, as indicated by decreasing the duration of immobility in tail suspension test and increasing the crossing number, rearing number and time in center in open field test. Accordingly, ICAB inhibited oxidative stress by decreasing malondialdehyde (MDA) level and increasing the antioxidant enzyme activity. ICAB also inhibited Pb-induced inflammation in brain, as indicated by decreasing the tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels. ICAB increased the expression levels of brain derived neurotrophic factor (BDNF) and the phosphorylation of cAMP-responsive element binding protein (CREB), phosphoinositide 3-kinases-protein kinase B (PI3K/AKT). Furthermore, ICAB decreased the levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), glycogen synthase kinase-3 beta (GSK-3β) and p38. Collectively, this study demonstrated that ICAB improved Pb-induced anxiety, depression, neuroinflammation and oxidative stress by regulating the BDNF signaling pathway.